Energy Transformation: Cellular Respiration Outline

1. Sources of cellular ATP2. Turning chemical energy of covalent bonds between C-C into

energy for cellular work (ATP)3. Importance of electrons and H atoms in oxidation-reduction

reactions in biological systems4. Cellular mechanisms of ATP generation5. The four major central metabolic pathways

Glycolysis- FermentationTransition step Krebs CycleElectron Transport chain and oxidative phosphorylation

4. Poisons of cellular respiration and their mechanisms of action.5. Use of biomolecules other than glucose as carbon skeletons &

energy sources

http://health.howstuffworks.com/sports-physiology3.htm

A cell has enough ATP to last for about three seconds

Necessary ATP is supplied to muscle cells by

1. Phosphagen system (8 to 10 seconds.)2. Glycogen-lactic acid system (90 seconds)- glucose3. Aerobic Respiration (unlimited)- glucose

Phosphagen system (muscle fibers)

(*) Arezki Azzi et al. Protein Sci 2004; 13: 575-585

• Creatine phosphate contains (a high-energy phosphate compound).

• Creatine kinase transfers the phosphate to ADP to form ATP.

Creatine-Phosphate (tri)

*

Creatine-Phosphate + ADP (Tri)

Creatine-Phosphate + ATP(Di)

Creatine Kinase

During cellular respiration the potential energy in the chemical bonds holding C atoms in organic molecules in turned into ATP.

In presence of oxygencomplete breakdown

C-C-C-C-C-C + O2……………… CO2 + H2O + ATPlarge amount

In absence of oxygenincomplete breakdown

C-C-C-C-C-C ……………… 2 C-C-C + ATPsmall amount

Cellular respiration: ATP is produced aerobically, in the presence of oxygen

Fermentation: ATP is produced anaerobically, in the absence of oxygen

Chemical bonds of organic molecules

Chemical bonds involve electrons of atoms

Electrons have energy

Chemical bonds are forms of potential energy

If a molecule loses an electron does it lose energy?

When a chemical bond is broken sometimes electrons can be released

• Oxidation: removal of electrons.• Reduction: gain of electrons.• Redox reaction: oxidation reaction paired with a

reduction reaction.

Oxidation-Reduction

The electrons associated with hydrogen atoms. Biological oxidations are often dehydrogenations

Soluble electron carriersNAD+, and FAD (ATP generation) NADP+ (biosynthetic reactions)

Electron Carriers in Biological Systems

Nicotinamide Adenine Dinucleotide (NAD+) a co-enzyme that acts as an electron shuttle (Niacin)

NAD+

Nicotinamide (oxidized form)

Dehydrogenase

2 e– + 2 H+2 e– + H+

NADH H+

H+

Nicotinamide (reduced form)

+ 2[H](from food)

+

Flavin Adenine Dinucleotide (FAD+) is another co-enzyme that acts as an electron shuttle (Vitamin B2)

In Metabolic pathwaysOxidation Reduction

• Energy loss or gain• Exergonic or endergonic• Catabolic or anabolic

In cells, energy is harvested from an energy source (organic molecule) by a series of coupled oxidation/reduction reactions (redox) known as the central metabolic pathways

becomes oxidized

becomes reduced

Dehydrogenase

Metabolic PathwaysLinear Pathways

Branched Pathways

Cyclic Pathways

An overview of the central metabolic pathways

• Glycolysis• Transition step• Tricarboxylic acid cycle (TCA or Krebs cycle)• The Electron Transport Chain and oxidative

phosphorylation

1. Oxidative phosphorylation/ Chemiosmosis

Mechanisms of ATP Generation during cellular respiration

• ADP and inorganic PO-4

• ATP synthase• Cellular respiration in mitochondria• Electron Transport Chain

2. Substrate-level phosphorylation

Generation of ATP

-Transfer of a high-energy PO4 from an organic molecule to ADP- Different enzymes- During glycolysis and theTCA or Krebs cycle

-

Glycolysis

• Multi – step breakdown of glucose into intermediates

• Turns one glucose (6-carbon) into two pyruvate (3-carbon) molecules

• Generates a small amount of ATP (substrate-level phosphorylation)

• Generates reducing power - NADH + H+

Figure 9.18 Pyruvate as a key juncture in catabolism

Fermentation

• An extension of glycolysis• Takes place in the absence of oxygen (anaerobic)• Regenerates NAD+ from NADH + H +

• ATP generated by substrate - level phosphorylation during glycolysis

• Does not use the Krebs cycle or ETC (no oxidative -phosphorylation)

• A diversity of end products produced (i.e. lactic acid, alcohols, etc.)

Figure 9.17a Fermentation

Figure 9.17b Fermentation

Figure 9.9 A closer look at glycolysis: energy investment phase

Figure 9.9 A closer look at glycolysis: energy payoff phase

Energy investment phase

Glucose

2 ATP used2 ADP + 2 P

4 ADP + 4 P 4 ATP formed

2 NAD+ + 4 e– + 4 H+

Energy payoff phase

2 NADH + 2 H+

2 Pyruvate + 2 H2O

Net2 Pyruvate + 2 H2O

2 ATP

2 NADH + 2 H+

Glucose

4 ATP formed – 2 ATP used

2 NAD+ + 4 e– + 4 H+

Glycolysis Citricacidcycle

Oxidative phosphorylation

ATPATPATP

The energy input and output of glycolysis

Transition step

• Under aerobic conditions, the pyruvate produced during glycolysis is directed to the mitochondrion.

• A multi-enzyme complex, spanning the 2 mitochondrial membranes, turns pyruvate (3-carbon) into Acetyl-CoA (2-carbon) and releases one CO2molecule

• Uses coenzyme A (Vit B derivative)• Generates reducing power NADH + H+

Figure 9.10 Conversion of pyruvate to acetyl CoA, the junction between glycolysis and the Krebs cycle

Krebs or TCA Cycle

• A cyclical pathway• Accepts – acetyl – CoA• Generates 2 – CO2 molecules (for every acetyl-CoA• Generates reducing power NADH + H+ and FADH2

• Generates a small amount of ATP (substrate-level phosphorylation)

A closer look at the Krebs cycle

Figure 9.12 A summary of the transition step and Krebs cycle

Figure 9.5 An introduction to electron transport chains

Electron Transport Chain and ATP generation

Electron transport chain:• membrane-embedded or

bound electron carriers• Mostly proteins with non-

protein groups.• NADH vs. FADH2

• No direct formation of ATP• Pumps H+ into the inter-

membrane space

Oxidative Phosphorylation and ATP generation

ATP Generation :• Membrane-embedded protein

complex , ATP synthase• Proton-motive force• Direct formation of ATP by

Chemiosmosis

Chemiosmosis: the coupling of the transport of H+ across membrane by facilitated diffusion with chemical reaction producing ATP

ATP Synthase Gradient: The Moviehttp://vcell.ndsu.edu/animations/at

pgradient/movie.htm

Chemiosmosis couples the electron transport chain to ATP synthesis

Certain poisons interrupt critical events in cellular respiration• Block the movement of electrons• Block the flow of H+ through ATP synthase• Allow H+ to leak through the membrane

H+

H+

H+

H+

H+

H+ H+ H+ H+

+2 H+

H+

H+H+

1 O22

H O2ADP + P ATP

NADHFADH2

NAD+

FAD

Rotenone Cyanide, carbon monoxide

Oligomycin

DNP

ATPSynthase

Electron Transport Chain Chemiosmosis

Energy yield: How many ATP molecules are generated during cellular respiration of a single glucose molecule?

Sources of cellular glucose

• glucose from food in the intestine• glycogen supplies in the muscles• breakdown of the Liver's glycogen into

glucose

The Catabolism of various food molecules

Beta oxidation

http://www.brookscole.com/chemistry_d/templates/student_resources/shared_resources/animations/carnitine/carnitine1.html

• Triglycerides consist of glycerol and fatty acids• Fatty acids broken down into through beta

oxidation

Simple lipids

Proteins

Protein Amino acidsExtracellular proteases

Krebs cycle and glycolysis Transition step

Deamination, decarboxylation,dehydrogenation Organic acid

Feedback control of cellular respiration

PhosphofructokinaseAllosteric enzymeActivity modulated by inhibitors and activatorsAdjustment of cellular respiration in response to demand

OXIDATIVE PHOSPHORYLATION(Electron Transport and Chemiosmosis)

Food, such as peanuts

Carbohydrates Fats Proteins

Sugars Glycerol Fatty acids Amino acids

Amino groups

Glucose G3P Pyruvate Acetyl CoA

CITRIC ACID CYCLE

ATP

GLYCOLYSIS

Food molecules provide raw materials for biosynthesis consuming ATP

ATP needed to drive biosynthesis

ATP

CITRIC ACID CYCLE

GLUCOSE SYNTHESIS G3P

Acetyl CoA Pyruvate Glucose

Amino groups

Amino acids Fatty acids

Glycerol Sugars

CarbohydratesFatsProteins

Cells, tissues, organisms